MYELIN

髓磷脂

• 批准号: 6267156
• 负责人: ALAN PETERS
• 金额: $ 19.13万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 1999-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6267156
• 关键词: Macaca mulatta; aging; axon; cognition; cognition disorders; electron microscopy; frontal lobe /cortex; hippocampus; magnetic resonance imaging; myelin; neural transmission; neuroanatomy; radioassay; retina; tritium; visual cortex; visual pathways

During the last grant period we examined several areas of the cerebral cortex of young (4 to 6 years of age) and old (over 25 years of age) rhesus monkeys and came to the conclusion that there is no significant loss of cortical neurons with age. However there are other significant changes both in the cortex and in the underlying white matter. The most obvious of these is a breakdown in the integrity of myelin. This is not demyelination in the sense that the axons are left bare, but a breakdown in the integrity of the sheats that might best be termed ~dysmyelination~. There is some evidence of axonal degeneration, but this is not pronounced in the cortex. Furthermore, in our study of the frontal cortex we found that there is a correlation between the extent of myelin breakdown and the performance of old monkeys on the delayed nonmatching to sample tasks. In addition, MCI scans of the cerebral hemispheres of our monkeys, show a loss of white matter, but not of gray matter, with age. And when the extent of loss of white matter is plotted against the behavioral performance of the monkeys, there is a significant correlation with the performance of the monkeys on the acquisition component of the delayed nonmatching to sample task. These results have lead us to believe that a breakdown in the integrity of myelin might underlie the cognitive deficits, since this would reduce the conduction rates along some axons and disrupt the timing of synaptic activity in neuronal circuits. Obviously, an in depth study of the effect of aging on myelin is important. We propose to continue MCI scans to obtain better data on the correlation between white matter loss and behavioral performance. In addition, we will use a new tritium quenching technique to determine whether myelin loss is more prevalent in some cortical areas that in others, and will correlate the results with the recorded behavior of the monkeys. Finally, we propose to examine the effect of aging on myelin sheaths by electron microscopy, to determine how sheaths break down, what size fibers are most affected, and whether the breakdown of the myelin occurs equally throughout the CNS, or whether it is more prominent in some fiber pathways than in others. For this purpose, we have chosen to examine the visual pathway, since this system offers a hierarchical system of fiber connections, as well as intracortical and extracortical connections, whose origins and terminations are well known.

在上一次资助期间，我们检查了大脑的几个区域 年轻（4至6岁）和老年（25岁以上）的皮质 恒河猴并得出结论：没有显着的 随着年龄的增长，皮质神经元会丧失。 然而还有其他 皮质和底层白色均发生显着变化 事情。 其中最明显的是完整性的崩溃 髓磷脂。 这并不是轴突脱髓鞘的意思 裸露，但护套的完整性可能会受到破坏 最好称为“髓鞘形成障碍”。 有一些轴突的证据 退化，但这在皮质中并不明显。 此外， 在我们对额叶皮层的研究中，我们发现有一个 髓磷脂分解程度与表现之间的相关性 老猴子关于样本任务延迟不匹配的问题。 在 此外，我们猴子大脑半球的 MCI 扫描显示 随着年龄的增长，白质会减少，但灰质不会减少。 而当 将白质损失的程度与行为进行绘制 猴子的表现与 猴子在获取部分的表现 延迟与样本任务不匹配。 这些结果引导我们 认为髓磷脂完整性的破坏可能是 认知缺陷，因为这会降低传导率 一些轴突并扰乱神经元突触活动的时间 电路。 显然，深入研究衰老对髓磷脂的影响是有必要的。 重要的。 我们建议继续 MCI 扫描以获得更好的数据 白质损失与行为表现之间的相关性。 此外，我们将使用一种新的氚淬火技术 确定髓鞘质损失是否在某些皮质区域更为普遍 在其他人中，并将结果与​​记录相关联 猴子的行为。 最后，我们建议检查一下效果 通过电子显微镜观察髓鞘的老化情况，以确定如何 鞘破裂，什么尺寸的纤维受影响最大，以及是否 髓磷脂的分解在整个中枢神经系统中同样发生，或者 它在某些纤维通路中是否比其他纤维通路中更突出。 为此，我们选择检查视觉通路，因为 该系统还提供了光纤连接的分层系统 作为皮质内和皮质外的连接，其起源和 终止是众所周知的。